Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

On staying grounded and avoiding Quixotic dead ends

The 15 articles in this special issue on The Representation of Concepts illustrate the rich variety of theoretical positions and supporting research that characterize the area. Although much agreement exists among contributors, much disagreement exists as well, especially about the roles of grounding and abstraction in conceptual processing. I first review theoretical approaches raised in these articles that I believe are Quixotic dead ends, namely, approaches that are principled and inspired but likely to fail. In the process, I review various theories of amodal symbols, their distortions of grounded theories, and fallacies in the evidence used to support them. Incorporating further contributions across articles, I then sketch a theoretical approach that I believe is likely to be successful, which includes grounding, abstraction, flexibility, explaining classic conceptual phenomena, and making contact with real-world situations. This account further proposes that (1) a key element of grounding is neural reuse, (2) abstraction takes the forms of multimodal compression, distilled abstraction, and distributed linguistic representation (but not amodal symbols), and (3) flexible context-dependent representations are a hallmark of conceptual processing

Antibiotic resistance and biofilm formation ability among coagulase-negative staphylococci in healthy individuals from Portugal

In the past few years the interest in coagulase-negative staphylococci (CoNS) species has significantly increased due to their impact on human health and disease. CoNS are common bacterial colonizers of the normal human microflora and usually have a benign relationship with the host.This work was funded by Fundacao para a Ciencia e a Tecnologia (FCT) and COMPETE grants PTDC/BIA-MIC/113450/2009 and FCOMP-01-0124-FEDER-014309

Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

Theories for influencer identification in complex networks

In social and biological systems, the structural heterogeneity of interaction networks gives rise to the emergence of a small set of influential nodes, or influencers, in a series of dynamical processes. Although much smaller than the entire network, these influencers were observed to be able to shape the collective dynamics of large populations in different contexts. As such, the successful identification of influencers should have profound implications in various real-world spreading dynamics such as viral marketing, epidemic outbreaks and cascading failure. In this chapter, we first summarize the centrality-based approach in finding single influencers in complex networks, and then discuss the more complicated problem of locating multiple influencers from a collective point of view. Progress rooted in collective influence theory, belief-propagation and computer science will be presented. Finally, we present some applications of influencer identification in diverse real-world systems, including online social platforms, scientific publication, brain networks and socioeconomic systems.Comment: 24 pages, 6 figure

The Secret to Successful User Communities: An Analysis of Computer Associates’ User Groups

This paper provides the first large scale study that examines the impact of both individual- and group-specific factors on the benefits users obtain from their user communities. By empirically analysing 924 survey responses from individuals in 161 Computer Associates' user groups, this paper aims to identify the determinants of successful user communities. To measure success, the amount of time individual members save through having access to their user networks is used. As firms can significantly profit from successful user communities, this study proposes four key implications of the empirical results for the management of user communities

White matter injury restoration after stem cell administration in subcortical ischemic stroke

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Introduction]: An animal model of subcortical ischemic stroke with white matter affectation was induced in rats by injection of endothelin-1. At 24 hours, 2 × 10 6 ADMSC were administered intravenously to the treatment group. Functional evaluation, lesion size, fiber tract integrity, cell death, proliferation, white matter repair markers (Olig-2, NF, and MBP) and NogoA were all studied after sacrifice (7 days and 28 days). ADMSC migration and implantation in the brain as well as proteomics analysis and functions of the secretome were also analyzed. [Results]: Neither ADMSC migration nor implantation to the brain was observed after ADMSC administration. In contrast, ADMSC implantation was detected in peripheral organs. The treatment group showed a smaller functional deficit, smaller lesion area, less cell death, more oligodendrocyte proliferation, more white matter connectivity and higher amounts of myelin formation. The treated animals also showed higher levels of white matter-associated markers in the injured area than the control group. Proteomics analysis of the ADMSC secretome identified 2,416 proteins, not all of them previously described to be involved in brain plasticity. [Conclusions]: White matter integrity in subcortical stroke is in part restored by ADMSC treatment; this is mediated by repair molecular factors implicated in axonal sprouting, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery after stroke.This study was supported by research grants PS12/01754, PI11/00909 and INVICTUS (RD12/0014) (Spanish Neurovascular Network), SAF2010-37926, ProteoRed-PT13/0001/0017 and a Sara Borrell postdoctoral fellowship (CD12/00706, to LOO) from Research Institute Carlos III, Ministry of Science and Innovation of Spain. Furthermore, TS (CP12/03121) and FC (CP14/00154) are recipients of a research contract from Miguel Servet Program of Instituto de Salud Carlos III-Peer Reviewe

The tailored activity program (TAP) to address behavioral disturbances in frontotemporal dementia: a feasibility and pilot study

Purpose: To explore the feasibility of implementing the Tailored Activity Program with a cohort of people with frontotemporal dementia and their carers (dyads). Methods: The Tailored Activity Program is an occupational therapy based intervention that involves working collaboratively with family carers and prescribes personalized activities for behavioral management in people with dementia. Twenty dyads randomized into the study (Tailored Activity Program: n = 9; Control: n = 11) were assessed at baseline and 4-months. Qualitative analyzes evaluated feasibility and acceptability of the program for the frontotemporal dementia cohort, and quantitative analyzes (linear mixed model analyzes, Spearman’s rho correlations) measured the impact of the program on the dyads. Results: The Tailored Activity Program was an acceptable intervention for the frontotemporal dementia dyads. Qualitative analyses identified five themes: “carer perceived benefits”, “carer readiness to change”, “strategies used by carer to engage person with dementia”, “barriers to the Tailored Activity Program uptake/implementation”, and “person with dementia engagement”. Quantitative outcomes showed an overall reduction of behavioral symptoms (F 18.34 = 8.073, p = 0.011) and maintenance of functional performance in the person with dementia (F 18.03 = 0.375, p = 0.548). Conclusions: This study demonstrates the potential for using an activity-based intervention such as the Tailored Activity Program in frontotemporal dementia. Service providers should recognize that while people with frontotemporal dementia present with challenging issues, tailored therapies may support their function and reduce their behavioral symptoms.Implications for rehabilitation The Tailored Activity Program is an occupational therapy based intervention that involves prescribing personalized activities for behavioral management in dementia. The Tailored Activity Program is an acceptable and feasible intervention approach to address some of the unique behavioral and functional impairments inherent in frontotemporal dementia

A comparison of weather variables linked to infectious disease patterns using laboratory addresses and patient residence addresses

Background: To understand the impact of weather on infectious diseases, information on weather parameters at patient locations is needed, but this is not always accessible due to confidentiality or data availability. Weather parameters at nearby locations are often used as a proxy, but the accuracy of this practice is not known. Methods: Daily Campylobacter and Cryptosporidium cases across England and Wales were linked to local temperature and rainfall at the residence postcodes of the patients and at the corresponding postcodes of the laboratory where the patient’s specimen was tested. The paired values of daily rainfall and temperature for the laboratory versus residence postcodes were interpolated from weather station data, and the results were analysed for agreement using linear regression. We also assessed potential dependency of the findings on the relative geographic distance between the patient’s residence and the laboratory. Results: There was significant and strong agreement between the daily values of rainfall and temperature at diagnostic laboratories with the values at the patient residence postcodes for samples containing the pathogens Campylobacter or Cryptosporidium. For rainfall, the R-squared was 0.96 for the former and 0.97 for the latter, and for maximum daily temperature, the R-squared was 0.99 for both. The overall mean distance between the patient residence and the laboratory was 11.9 km; however, the distribution of these distances exhibited a heavy tail, with some rare situations where the distance between the patient residence and the laboratory was larger than 500 km. These large distances impact the distributions of the weather variable discrepancies (i.e. the differences between weather parameters estimated at patient residence postcodes and those at laboratory postcodes), with discrepancies up to ±10 °C for the minimum and maximum temperature and 20 mm for rainfall. Nevertheless, the distributions of discrepancies (estimated separately for minimum and maximum temperature and rainfall), based on the cases where the distance between the patient residence and the laboratory was within 20 km, still exhibited tails somewhat longer than the corresponding exponential fits suggesting modest small scale variations in temperature and rainfall. Conclusion: The findings confirm that, for the purposes of studying the relationships between meteorological variables and infectious diseases using data based on laboratory postcodes, the weather results are sufficiently similar to justify the use of laboratory postcode as a surrogate for domestic postcode. Exclusion of the small percentage of cases where there is a large distance between the residence and the laboratory could increase the precision of estimates, but there are generally strong associations between daily weather parameters at residence and laboratory